The proposed investigation is directed toward elucidating characteristics and mechanisms of diabetic peripheral neuropathy. To devise strategies for prevention and treatment of this most debilitating complication it is necessary to understand the underlying biochemical abnormalities. In addition, an understanding of the relationship between peripheral neuropathy and diabetic amyotrophy will be studied. The principal method to be used in studying the neuropathy will be measurements of axonal transport of enzymes. Fast and slow components as well as retrograde transport will be measured as an indication of the viability of the sciatic and vagus nerves. A series of in vitro and in vivo methods will be used to assess abnormal transport in experimentally diabetic rats and in galactose-intoxicated rats. The latter model has been used to investigate the involvement of toxic sugar metabolites in diabetic complications. Results of these studies will be used to design treatment modes for peripheral nerve disease. Similar experiments will demonstrate mechanisms of muscle pathology. Changes in the enzyme acetylcholinesterase will be used as an indication of muscle dysfunction in diabetic and galactosemic rats. Those abnormalities that can be reproduced in galactosemic rats will be considered as potentially treatable with aldose reductase inhibiting drugs.